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Acetylcholine exerts inhibitory and excitatory actions on mouse ileal pacemaker activity: role of muscarinic versus nicotinic receptors.
Am J Physiol Gastrointest Liver Physiol. 2020 Jul 01; 319(1):G97-G107.AJ

Abstract

The effect of acetylcholine (ACh) on pacemaking and spontaneous contractions in the gastrointestinal tract is not well characterized. The current study aims to profile the effect of several muscarinic and nicotinic receptor agonists and antagonists on pacemaker potentials in the ICR mouse ileum. Pacemaker potentials of whole thickness mouse ileal segments were recorded extracellularly using a 60-channel microelectrode array (MEA) platform. A spatiotemporal analysis integrated the frequency, amplitude, and velocity measurements of pacemaker currents. Comparative data were obtained by recording spontaneous smooth muscle tone in a conventional organ bath. On the MEA, ACh (0.3-300 μM) and bethanechol (0.3-300 μM) significantly reduced ileal pacemaker potentials. The inhibitory effect of ACh was mimicked by donepezil (300 μM) but not nicotine (0.3-7 mM). Atropine (300 μM), but not hexamethonium (300 μM), reversed the inhibitory actions of ACh and bethanechol and revealed excitatory properties manifested as increases in pacemaker frequency. A spatial analysis also revealed that atropine, but not hexamethonium, reversed the ACh-induced distortion of pacemaker propagation activity. Atropine (0.001-3 mM) and hexamethonium (0.3-7 mM) alone were inactive. In the organ bath, ACh (300 nM) and bethanechol (30 μM) induced ileal tonic contractions, while inhibiting basal spontaneous contractions at 300 μM. Atropine (1 μM), but not hexamethonium (1-300 μM), reversed both the tonic contractions and the inhibition of the spontaneous contractions of ACh and bethanechol and revealed an excitatory effect manifested as an increasing in the frequency of contractions. Muscarinic, but not nicotinic, receptors appear to mediate the inhibitory actions of ACh on mouse ileal pacemaker potentials.NEW & NOTEWORTHY The study discovered an acute action of acetylcholine on pacemaker potentials that is mediated by muscarinic receptors on the mouse ileum. Bethanechol, but not nicotine, mimicked the inhibitory actions of acetylcholine on pacemaker potentials. Atropine, but not hexamethonium, reversed the inhibitory actions of acetylcholine. When introduced after acetylcholine, atropine exhibited excitatory actions that increased the pacemaker frequency. Acetylcholine and bethanechol distorted the propagation activity and pattern, and this was also reversed by atropine. These actions of acetylcholine on pacemaker potentials may contribute to pathophysiology in bowel diseases.

Authors+Show Affiliations

School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, People's Republic of China.Auckland Bioengineering Institute, University of Auckland, Auckland, New Zealand.School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong Special Administrative Region, People's Republic of China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32475128

Citation

Liu, Julia Yuen Hang, et al. "Acetylcholine Exerts Inhibitory and Excitatory Actions On Mouse Ileal Pacemaker Activity: Role of Muscarinic Versus Nicotinic Receptors." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 319, no. 1, 2020, pp. G97-G107.
Liu JYH, Du P, Rudd JA. Acetylcholine exerts inhibitory and excitatory actions on mouse ileal pacemaker activity: role of muscarinic versus nicotinic receptors. Am J Physiol Gastrointest Liver Physiol. 2020;319(1):G97-G107.
Liu, J. Y. H., Du, P., & Rudd, J. A. (2020). Acetylcholine exerts inhibitory and excitatory actions on mouse ileal pacemaker activity: role of muscarinic versus nicotinic receptors. American Journal of Physiology. Gastrointestinal and Liver Physiology, 319(1), G97-G107. https://doi.org/10.1152/ajpgi.00003.2020
Liu JYH, Du P, Rudd JA. Acetylcholine Exerts Inhibitory and Excitatory Actions On Mouse Ileal Pacemaker Activity: Role of Muscarinic Versus Nicotinic Receptors. Am J Physiol Gastrointest Liver Physiol. 2020 Jul 1;319(1):G97-G107. PubMed PMID: 32475128.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Acetylcholine exerts inhibitory and excitatory actions on mouse ileal pacemaker activity: role of muscarinic versus nicotinic receptors. AU - Liu,Julia Yuen Hang, AU - Du,Peng, AU - Rudd,John Anthony, Y1 - 2020/06/01/ PY - 2020/6/2/pubmed PY - 2020/6/2/medline PY - 2020/6/2/entrez KW - acetylcholine KW - gastrointestinal tract KW - interstitial cells of Cajal KW - microelectrode array KW - pacemaker potentials SP - G97 EP - G107 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am. J. Physiol. Gastrointest. Liver Physiol. VL - 319 IS - 1 N2 - The effect of acetylcholine (ACh) on pacemaking and spontaneous contractions in the gastrointestinal tract is not well characterized. The current study aims to profile the effect of several muscarinic and nicotinic receptor agonists and antagonists on pacemaker potentials in the ICR mouse ileum. Pacemaker potentials of whole thickness mouse ileal segments were recorded extracellularly using a 60-channel microelectrode array (MEA) platform. A spatiotemporal analysis integrated the frequency, amplitude, and velocity measurements of pacemaker currents. Comparative data were obtained by recording spontaneous smooth muscle tone in a conventional organ bath. On the MEA, ACh (0.3-300 μM) and bethanechol (0.3-300 μM) significantly reduced ileal pacemaker potentials. The inhibitory effect of ACh was mimicked by donepezil (300 μM) but not nicotine (0.3-7 mM). Atropine (300 μM), but not hexamethonium (300 μM), reversed the inhibitory actions of ACh and bethanechol and revealed excitatory properties manifested as increases in pacemaker frequency. A spatial analysis also revealed that atropine, but not hexamethonium, reversed the ACh-induced distortion of pacemaker propagation activity. Atropine (0.001-3 mM) and hexamethonium (0.3-7 mM) alone were inactive. In the organ bath, ACh (300 nM) and bethanechol (30 μM) induced ileal tonic contractions, while inhibiting basal spontaneous contractions at 300 μM. Atropine (1 μM), but not hexamethonium (1-300 μM), reversed both the tonic contractions and the inhibition of the spontaneous contractions of ACh and bethanechol and revealed an excitatory effect manifested as an increasing in the frequency of contractions. Muscarinic, but not nicotinic, receptors appear to mediate the inhibitory actions of ACh on mouse ileal pacemaker potentials.NEW & NOTEWORTHY The study discovered an acute action of acetylcholine on pacemaker potentials that is mediated by muscarinic receptors on the mouse ileum. Bethanechol, but not nicotine, mimicked the inhibitory actions of acetylcholine on pacemaker potentials. Atropine, but not hexamethonium, reversed the inhibitory actions of acetylcholine. When introduced after acetylcholine, atropine exhibited excitatory actions that increased the pacemaker frequency. Acetylcholine and bethanechol distorted the propagation activity and pattern, and this was also reversed by atropine. These actions of acetylcholine on pacemaker potentials may contribute to pathophysiology in bowel diseases. SN - 1522-1547 UR - https://www.unboundmedicine.com/medline/citation/32475128/Acetylcholine_Exerts_Inhibitory_and_Excitatory_Actions_on_Mouse_Ileal_Pacemaker_Activity:_The_Role_of_Muscarinic_versus_Nicotinic_Receptors L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00003.2020?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -
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